Moduli-Space Dynamics of Noncommutative Abelian Sigma-Model Solitons

In the noncommutative (Moyal) plane, we relate exact U(1) sigma-model solitons to generic scalar-field solitons for an infinitely stiff potential. The static k-lump moduli space C^k/S_k features a natural K"ahler metric induced from an embedding Grassmannian. The moduli-space dynamics is blind against adding a WZW-like term to the sigma-model action and thus also applies to the integrable U(1) Ward model. For the latter's two-soliton motion we compare the exact field configurations with their supposed moduli-space approximations. Surprisingly, the two do not match, which questions the adiabatic method for noncommutative solitons.Comment: 1+15 pages, 2 figures; v2: reference added, to appear in JHE

Checking Properties Described by State Machines: On Synergy of Instrumentation, Slicing, and Symbolic Execution

We introduce a novel technique for checking properties described by finite state machines. The technique is based on a synergy of three well-known methods: instrumentation, program slicing, and symbolic execution. More precisely, we instrument a given program with a code that tracks runs of state machines representing various properties. Next we slice the program to reduce its size without affecting runs of state machines. And then we symbolically execute the sliced program to find real violations of the checked properties, i.e. real bugs. Depending on the kind of symbolic execution, the technique can be applied as a stand-alone bug finding technique, or to weed out some false positives from an output of another bug-finding tool. We provide several examples demonstrating the practical applicability of our technique.Představujeme novou techniku pro ověřování vlastností popsaných konečně-stavovými stroji. Tato technika je založena na synergii tří známých metod: instrumentace, prořezání programu a symbolické vykonání. Přesněji, instrumentujeme daný program kódem, který sleduje běh stavových strojů představujících různé vlastnosti. Dále program prořežeme, abychom zmenšili jeho velikost při zachování běhů stavových strojů. Nakonec prořezaný program symbolicky vykonáme, abychom našli skutečné porušení ověřovaných vlastností, t.j. skutečné chyby. Podle použitého druhu symbolického vykonání může být tato technika použita jako samostatná metoda pro detekci chyb nebo k vytřídění některých falešných hlášení z výstupu jiných nástrojů pro detekci chyb. Poskytujeme několik příkladů, které dokumentují praktickou použitelnost naší techniky

Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function

The glycocalyx component and sialomucin podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumor types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL high and low surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipulated cells or those with different surface levels of PODXL define that this axis controls metastasis in vivo. Clinically, interplay between PODXL-GAL3 stratifies prostate cancer patients with poor outcome. Our studies define the molecular mechanisms and context in which PODXL promotes invasion and metastasis

Amygdala responses to emotional faces in twins discordant or concordant for the risk for anxiety and depression.

Background: Functional brain imaging studies have shown deviant amygdala responses to emotional stimuli in subjects suffering from anxiety and depressive disorder, but both hyperactivity and hypoactivity compared to healthy controls have been reported. To account for these discrepant findings, we hypothesize that genetic and environmental risk factors differently impact on amygdala functioning. Methods: To test this hypothesis, we assessed amygdala responses to an emotional faces paradigm during functional magnetic resonance imaging in monozygotic twin pairs discordant for the risk of anxiety and depression (n = 10 pairs) and in monozygotic twin pairs concordant for high (n = 7 pairs) or low (n = 15 pairs) risk for anxiety and depression. Results: Main effects (all faces vs. baseline) revealed robust bilateral amygdala activity across groups. In discordant twins, increased amygdala responses were found for negatively valenced stimuli (angry/anxious faces) in high-risk twins compared to their low-risk co-twins. In contrast, concordant high-risk pairs revealed blunted amygdala reactivity to both positive and negative faces compared with concordant low-risk pairs. Post-hoc analyses showed that these findings were independent of 5-HTTLPR genotype. Conclusions: Our findings indicate amygdala hyperactivity in subjects who are at high risk for anxiety and depression through environmental factors and amygdala hypoactivity in those at risk mainly through genetic factors. We suggest that this result reflects a difference in baseline amygdala activation in these groups. Future imaging studies on anxiety and depression should aim to avoid admixture of subjects who are at genetic risk with those at risk due to environmental factors. © 2008 Elsevier Inc. All rights reserved

Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort

We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ϵ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure

Cell Specific eQTL Analysis without Sorting Cells

The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn’s disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus

The sequence of structural, functional and cognitive changes in multiple sclerosis

Background: As disease progression remains poorly understood in multiple sclerosis (MS), we aim to investigate the sequence in which different disease milestones occur using a novel data-driven approach. Methods: We analysed a cohort of 295 relapse-onset MS patients and 96 healthy controls, and considered 28 features, capturing information on T2-lesion load, regional brain and spinal cord volumes, resting-state functional centrality (“hubness”), microstructural tissue integrity of major white matter (WM) tracts and performance on multiple cognitive tests. We used a discriminative event-based model to estimate the sequence of biomarker abnormality in MS progression in general, as well as specific models for worsening physical disability and cognitive impairment. Results: We demonstrated that grey matter (GM) atrophy of the cerebellum, thalamus, and changes in corticospinal tracts are early events in MS pathology, whereas other WM tracts as well as the cognitive domains of working memory, attention, and executive function are consistently late events. The models for disability and cognition show early functional changes of the default-mode network and earlier changes in spinal cord volume compared to the general MS population. Overall, GM atrophy seems crucial due to its early involvement in the disease course, whereas WM tract integrity appears to be affected relatively late despite the early onset of WM lesions. Conclusion: Data-driven modelling revealed the relative occurrence of both imaging and non-imaging events as MS progresses, providing insights into disease propagation mechanisms, and allowing fine-grained staging of patients for monitoring purpose

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available